PB2259: THE NEW PD-1 INHIBITOR PROLGOLIMAB IN THE TREATMENT OF PATIENTS WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN’S LYMPHOMA
Authors: Anastasia Semenova, Shpirko Valeria, Gayane Tumyan, Arman Arakelyan, Timur Valiev, Sergei Lepkov, Galina Petrova, Elena Demina, Evgenia Paramonova, Daria Tupitsyna, Julia Kluchagina, Danila Lifentsev, Dzhelil Shevketovich
Journal: HemaSphere (2023)

Topic: 17. Hodgkin lymphoma - Clinical Background: Despite high cure rates with frontline therapy for classical Hodgkin lymphoma (cHL), approximately 30% of patients (pts) have relapsed or primary refractory disease (r/r). Autologous hematopoietic stem cell transplantation (autoHSCT) is the standard of care r/r cHL, unfortunately, only 50% of pts can be cured after auto-HSCT - some of the them develop refractory to second-line therapy (DHAP, ICE) or progress after transplantation. Programmed cell death receptor inhibitors (nivolumab, pembrolizumab) is effective treatment option for r/r HL. Prolgolimab is a human monoclonal antibody, a PD1 inhibitor of the immunoglobulin G1 isotype. Binding to the PD-1 receptor, it`s blocks interaction with the PD-L1 and PD-L2 ligands and reactivates cytotoxic T-lymphocytes. It is manufactured by JSC BIOCAD, Russia and approved for the treatment of adult pts with unresectable or metastatic melanoma in Russia. Aims: This analysis was aimed to determine the efficacy and safety of combination novel agent prolgolimab and DHAP salvage chemotherapy before autoHSCT in pts with r/r HL. Methods: A total of 4 pts with HL (3 women, median age - 29.5 years, range 22-39) relapsed (3 pts) or were refractory to one of the previous front-line therapy regimes (1 pts treated with ABVD, 3 - BEACOPP-14); 2 pts previously received radiation therapy. The median duration of the first response was 29 months (range 12–47 months). At relapse, 3 patients were administered brentuximab vedotin monotherapy at 1.8 mg/kg every 21 days (median 10; range 8-14 doses), but had disease progression. Results: The all pts receiving 2 cycles of prolgolimab 1 mg/kg monotherapy every 2 weeks (median dose 72.3 mg, range 48–118 mg). No infusion or immune-related reactions were observed. This treatment was followed by 2-3 cycles of DHAP chemotherapy in combination with prolgolimab 1 mg/kg. Two out of 4 patients had an isolated increase in the activity of hepatic transaminases (ALT, AST) to 2-3 x upper limit of normal (ULN). This complication was not associated with prolgolimab monotherapy. At the next stage, PET scanning was used to evaluate the effect. All 4 patients achieved an objective response, including 3 CR and 1 PR, which are still observed at a median follow-up of 7 months. Chemo mobilization with etoposide performed, the median number of collected CD34+ cells was 5.6 x10^6/kg. As of February 2023, 1 respondent has received autoHSCT, 2 pts are being evaluated prior to autoHSCT. Summary/Conclusion: Previously published retrospective results indicate that immunotherapy with PD-1 inhibitors (nivolumab, pembrolizumab), which has been used in the treatment of r/refractory HL in the Russian Federation since 2017, is highly effective in combination with chemotherapy (approximately 70%) and safe in terms of toxicity. The most common grade 3-4 adverse events were increased lipase levels (up to 5% of cases), neutropenia (3%), diarrhea (1%), rash (1%), autoimmune complications (<1%). Our results demonstrate that the combination of the new PD-1 inhibitor prolgolimab and DHAP can be synergistic, highly effective, and extremely safe, serving as a potential bridge to consolidation therapy. Keywords: Hodgkin’s lymphoma, Immunotherapy, Treatment, relapsed/refractory